Kiyoshi Takagi

Finite element simulation of blood flow in the cerebral artery

Abstract The purpose of the paper is to develop a numerical simulation system for the clinical study of a cerebral aneurysm. This paper presents the system, which consists of three processes: pre-processing, numerical simulation and post-processing. In the pre-processing process, the three-dimensional solid model was constructed from the computed tomography (CT) angiography raw data. The finite element method (FEM) is used in order to simulate flow in a complicated geometry. The simulation is conducted to investigate hemodynamics of blood flow in the carotid siphon under real flow conditions measured by Doppler ultrasound velocimetry technique. The results are visualized for a better understanding of the flow characteristics such as distributions of the flow pattern and the wall shear stress in the carotid siphon.

Atrophy of the ipsilateral substantia nigra following middle cerebral artery occlusion in the rat

Following occlusion of the left middle cerebral artery in the rat, marked atrophy was observed in the ipsilateral substantia nigra in and after the second week. The mechanism of this neuropathological change in the substantia nigra, which is remote from the site of infarction, may be explained by transsynaptic, neurotransmitter-mediated disinhibition as a result of infarction of the striatum.

Local hemodynamic changes during transient middle cerebral artery occlusion and recirculation in the rat: a [14C]iodoantipyrine autoradiographic study

We evaluated acute alterations of local cerebral perfusion following 30 min of transient right proximal middle cerebral artery (MCA) clip-occlusion in the rat and following two intervals of postischemic reperfusion. Local cerebral blood flow (lCBF) was assessed by [14C]iodoantipyrine autoradiography. Brain temperature was controlled at 35.5-36.5 degrees C throughout the experiment. We measured lCBF in four groups of rats: (a) sham-operated controls (n = 5), (b) following 30 min MCA occlusion (n = 5), (c) following 30 min of MCA occlusion with 15-min reperfusion (n = 6) and (d) following 30 min of MCA with 120-min reperfusion (n = 6). lCBF was measured in seven regions of the ischemic and non-ischemic hemispheres. MCA occlusion induced an ipsilateral reduction of lCBF, which was most severe in the parietal cortex (8.4 +/- 4.0% of control, mean +/- S.D.), and dorsolateral caudoputamen (20.0 +/- 13.4% of control). lCBF in the non-ischemic hemisphere and in ipsilateral regions lying outside the MCA territory also decreased significantly. lCBF recovery was incomplete when assessed following only 15 min of reperfusion. Reperfusion of 120 min led to return of cortical CBF to control levels, but lCBF in the caudoputamen remained depressed (50-55% of control values). Caudoputaminal CBF and cortical CBF values were highly correlated with one another under normal and ischemic conditions, but this correlation was disrupted following reperfusion. On the basis of these results, we speculate that, if a means were found to enhance the early recovery of lCBF following transient ischemia, this might expand the therapeutic window of opportunity for the institution of other neuroprotective strategies.

Body Temperature in Acute Stroke

To the Editor: I read with great interest the recent article by Boysen and Christensen1 on body temperature. Their study is probably the first to have described the hourly changes in body temperature after onset of stroke and intracerebral hemorrhage. Although they used paracetamol for the patient with a body temperature >37°C, the pattern was very similar to that observed in an animal experiment.2 This suggests that the basic mechanisms underlying the temperature …

The Neuroprotective Effect of the Novel Noncompetitive NMDA Antagonist, FR115427 in Focal Cerebral Ischemia in Rats

The present study was carried out to compare the neuroprotective effect of the novel noncompetitive NMDA antagonist, FR115427, with that of (+)MK-801 in rat focal cerebral ischemia. Focal cerebral ischemia was produced by permanent occlusion of the left middle cerebral artery (MCA). Drugs were administered intraperitoneally immediately after ischemia and once a day for 6 successive days. FR115427 (10 mg/kg, i.p.) significantly improved neurologic deficit at 1 day after ischemia and reduced total infarct volume (54%) at 7 days after ischemia. Although FR115427 (10 mg/kg, s.c.) produced neuronal vacuolization similar to (+)MK-801, FR115427 did not produce adverse effects such as a loss of body weight, mortality, and hypothermia, in contrast to (+)MK-801. These results suggest that FR115427 may be useful in the treatment of stroke.

Post-ischemic administration of DY-9760e, a novel calmodulin antagonist, reduced infarct volume in the permanent focal ischemia model of spontaneously hypertensive rat

Abstract We assessed the effect of a novel calmodulin antagonist, DY-9760e (3-[2-[4-(3-chloro-2-methylphenyl)-1-piperazinyl]ethyl]-5,6-dimethoxy-1-(4-imidazolylmethyl)-1 H-indazole dihydrochloride 3.5 hydrate) in a spontaneously hypertensive rat (SHR) permanent focal cerebral ischemia. In experiment I, the left middle cerebral artery was permanently occluded in 62 SHRs. DY-9760e (0.5 mg kg-1 h-1) or vehicle alone were administered continuously i.v. for 6 h, beginning 0, 30, or 60 min after the arterial occlusion. The infarct volume was measured 24 h of ischemia. In experiment II, the effect of DY-9760e on CBF was assessed in 10 SHRs. Administration without a delay resulted in a mean infarct volume of 166.7 ± 21.0 mm3 (vehicle; n = 10) and 125.1 ± 31.8 mm3 (DY-9760e; n = 9). Administration with a 30 min delay resulted in a mean infarct volume of 173.2 ± 32.4 mm3 (vehicle; n = 12) and 143.3 ± 35.3 mm3 (DY-9760e; n = 11). Dy-9760e significantly reduced the infarct under these conditions (p < 0.05). The administration with a 60 min delay failed to reduce the infarct. DY-9760e had no effect on the CBF. Continuous i.v. administration of DY-9760e reduced infarct volume in a SHR permanent focal ischemia without affecting ischemic CBF. [Neurol Res 2001; 23: 662-668]

Cisternal washing therapy for the prevention of cerebral vasospasm following aneurysmal subarachnoid hemorrhage.

Cerebral vasospasm is still one of the major causes of mortality and morbidity (M & M) in patients with subarachnoid hemorrhage (SAH) [1]. In spite of intense and extensive investigation over the past four decades, the optimal treatment of cerebral vasospasm has not yet been established. Clinical studies have clearly demonstrated the relationship between the location and volume of the subarachnoid clots and the incidence, distribution, and severity of vasospasm [3, 4, 11]. In 1988, Kodama et al reported that cisternal irrigation therapy with urokinase and ascorbic acid was effective in preventing cerebral vasospasm [5]. In 1990, Suzuki et al demonstrated that head-shaking method enhanced the fibrinolysis in cisternal irrigation [10]. In January 1994, we combined these two methods in order to achieve better outcome in Fisher CT group 3 patients and started cisternal irrigation therapy with urokinase combined with head-shaking, i.e., cisternal washing therapy.

Biosimulation and Visualization

Abstract: Hemodynamics plays an important role in cardiovascular disorders, and the authors are applying numerical and experimental studies of cerebrovascular blood flow to the creation and rupture of cerebral aneurysms. In particular, this study aims to investigate the effects of cerebrovascular geometry on hemodynamics, such as flow pattern, wall shear stress distribution, and pressure. This report consists mainly of two parts: numerical study of blood flow in the artery extracted from computer tomography data, and numerical and experimental studies of a curved pipe model. The simulation was conducted by using a finite element method; the experiment was conducted by particle imaging velocimetry. Numerical and experimental results are compared and both show similar secondary flow behavior.

Pituitary apoplexy as a consequence of lymphocytic adenohypophysitis in a pregnant woman: a case report.

Abstract Objective and importance: A patient with pituitary apoplexy resulting from lymphocytic adenohypophysitis, which caused visual disturbance during pregnancy, is described. This is the first report of such case. Clinical presentation: A 23-year-old primigravida in her 25th week of gestation experienced headache and bitemporal hemianopsia of sudden onset. Magnetic resonance imaging (MRI) revealed a large pituitary mass with intratumoral hemorrhage. Although conservative treatment with intravenous glycerol improved the symptoms partially, the visual symptoms worsened again 6 weeks later. After delivering a girl by scheduled caesarean section her visual symptoms improved. Despite the symptomatic improvement, MRI showed the chiasmatic compression by the enlarged pituitary gland had not changed. Therefore, trans-sphenoidal surgery to decompress the chiasm was performed. Necrotic tissue was seen exuding behind the enlarged pituitary gland and adenohypophysitis with bleeding (apoplexy) was diagnosed histologically. After follow-up for 40 months, she was doing well without any visual or neurological deficits. Conclusion: Although relatively rare, pituitary apoplexy as a consequence of lymphocytic adenohypophysitis should be borne in mind when a pregnant woman presents with headache and visual disturbance of sudden onset.

Animal Models Used in Cerebral Ischemia and Stroke Research

The central nervous system (CNS) is extremely vulnerable to ischemia. In humans, the brain accounts for approx 2% of body weight, but receives about 15% of cardiac output. The amounts of energy metabolites (glucose and glycogen) and oxygen stored in the brain are so small that cessation of blood supply for only a few minutes leads to severe CNS damage. This vulnerability of the CNS mainly derives from the vulnerability of neurons, the major component of the CNS. Therefore, many therapeutic modalities have been developed to protect neurons from ischemic damage. In this sense, cultured neurons (in vitro model) are enough to test the efficacy of a therapy. However, the results of such tests indicate only the level of cytotoxicity of a therapy. The cultured neurons never show neurological deficits. Ischemic insult to the human CNS may lead to a wide variety of signs and symptoms, from death to very slight neurological deficits. Rational therapies for cerebral ischemia should be established on a detailed understanding of the pathomechanisms involved. This is why we need experimental stroke models.